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Case Reports
. 2023 Oct;191(10):2647-2650.
doi: 10.1002/ajmg.a.63345. Epub 2023 Jul 14.

Revisiting the diagnosis of Gaucher disease in a family with multiple GBA1 variants

Emory Ryan  1 , Nahid Tayebi  1 , Andrea D'Souza  1 , Grisel Lopez  1 , Jens Lichtenberg  1 , Ellen Sidransky  1
Affiliations
Case Reports

Revisiting the diagnosis of Gaucher disease in a family with multiple GBA1 variants

Emory Ryan et al. Am J Med Genet A. 2023 Oct.

Abstract

Our ability to identify different variants in GBA1, the gene mutated in the lysosomal storage disorder Gaucher disease (GD), has greatly improved. We describe a multigenerational family with type 1 GD initially evaluated over three decades ago. Re-evaluating both the genotype and phenotype, we determined that one family member with genotype N370S/T369M (p.N409S/p.T408M), was likely erroneously diagnosed with GD. This case substantiates that GBA1 variant T369M, while mildly reducing glucocerebrosidase activity, does not result in GD. The observation has clinical relevance as cases with this genotype will increasingly be ascertained through screening programs in newborns and in movement disorder clinics.

Keywords: GBA1; Gaucher disease; T369M; genotyping.

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References

REFERENCES

    1. Balwani, M., Grace, M. E., & Desnick, R. J. (2011). Gaucher disease: When molecular testing and clinical presentation disagree -the novel c.1226A>G(p.N370S) - RecNcil allele. Journal of Inherited Metabolic Disease, 34(3), 789-793. https://doi.org/10.1007/s10545-011-9307-7
    1. Cullufi, P., Tabaku, M., Beetz, C., Tomori, S., Velmishi, V., Gjikopulli, A., Bauer, P., Wirth, S., & Rolfs, A. (2019). Comprehensive clinical, biochemical and genetic screening reveals four distinct GBA genotypes as underlying variable manifestation of Gaucher disease in a single family. Molecular Genetics and Metabolism Reports, 21, 100532. https://doi.org/10.1016/j.ymgmr.2019.100532
    1. Dardis, A., Michelakakis, H., Rozenfeld, P., Fumic, K., Wagner, J., Pavan, E., Fuller, M., Revel-Vilk, S., Hughes, D., Cox, T., Aerts, J., & International Working Group of Gaucher Disease (IWGGD). (2022). Patient centered guidelines for the laboratory diagnosis of Gaucher disease type 1. Orphanet Journal of Rare Diseases, 17(1), 442. https://doi.org/10.1186/s13023-022-02573-6
    1. Hodanova, K., Melkova, Z., Horowitz, M., & Hrebicek, M. (2003). Transient expression of wild-type and mutant glucocerebrosidases in hybrid vaccinia expression system. European Journal of Human Genetics, 11(5), 369-374. https://doi.org/10.1038/sj.ejhg.5200974
    1. Mallett, V., Ross, J. P., Alcalay, R. N., Ambalavanan, A., Sidransky, E., Dion, P. A., Rouleau, G. A., & Gan-Or, Z. (2016). GBA p.T369M substitution in Parkinson disease: Polymorphism or association? A meta-analysis. Neurology Genetics, 2(5), e104. https://doi.org/10.1212/NXG.0000000000000104

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